Abstract

OBJECTIVE:

To provide current and emerging evidence on oral contraceptives and the risk of venous thromboembolism.

EVIDENCE:

Articles published in English from 2005 were retrieved through searches of PubMed and Medline, using the following terms: venous thromboembolism, VTE, contraception, oral contraceptives, hormonal contraception. Results were restricted to systematic reviews, randomized control trials/controlled clinical trials, and observational studies. Searches were updated on a regular basis and incorporated in the guideline to May 2010. Grey (unpublished) literature was identified through searching the websites of health technology assessment and health technology assessment-related agencies, clinical practice guideline collections, clinical trial registries, and national and international medical specialty societies.

VALUES:

The quality of evidence was rated using the criteria described by the Canadian Task Force on Preventive Health Care (Table). SUMMARY STATEMENTS: 1. Modern oral contraceptives offer highly effective contraception and a range of non-contraceptive benefits. (I) 2. Venous thromboembolism, although rare, remains one of the serious adverse consequences of hormonal contraception. Best evidence indicates that venous thromboembolism rates in non-users of reproductive age approximate 4-5/10 000 women per year; rates in oral contraceptive users are in the range of 9-10/10 000 women per year. For comparison, venous thromboembolism rates in pregnancy approach 29/10 000 overall and may reach 300-400/10 000 in the immediate postpartum period. (II-1) 3. Research demonstrates that oral contraceptives with ≤ 35 µg of ethinyl estradiol carry a lower risk of venous thromboembolism than oral contraceptives with 50 µg. (II-2) Although preliminary data suggest a possible further reduction in venous thromboembolism with oral contraceptives with < 35 µg ethinyl estradiol, robust data to support this conclusion are presently lacking. 4. Recent contradictory evidence and the ensuing media coverage of the venous thromboembolism risk attributed to the progestin component of certain newer oral contraceptive products have led to fear and confusion about the safety of oral contraceptives in general and drospirenone-containing oral contraceptives in particular. "Pill scares" of this nature have occurred in the past, with panic stopping of the pill, increased rates of unplanned pregnancy, and no subsequent decrease in venous thromboembolism rates. (II-3) 5. Two high quality research studies that addressed the venous thromboembolism risk associated with various oral contraceptives found comparable venous thromboembolism rates with drospirenone-containing oral contraceptives and other approved products. (II-1) 6. Two reports suggesting an increased risk of venous thromboembolism with drospirenone-containing oral contraceptives have significant methodological flaws that render their conclusions suspect. It seems likely that residual confounding could have distorted both the results and the conclusions of these reports. (II-3).